Treponema pallidum is the etiologic agent of syphilis. Critical studies designed to elucidate the virulence determinants of this pathogenic spirochete, as well as the pathogenesis of this serious disease, are tremendously hindered by the inability to culture this bacterium in vitro. We propose to partially circumvent this problem by establishing in Escherichia coli K-12 colony banks representative of the entire T. pallidum genome. These colony banks will be screened, using both rabbit and human syphilitic serum, for E. coli clones expressing T. pallidum surface proteins. Our preliminary studies indicate that this is a feasible approach. We also plan to obtain monoclonal antibodies directed against various T. pallidum surface proteins. Together, these two approaches should provide us with a variety of tools for the identification of key treponemal proteins that mediate the infectious process and/or have an important role in the immune response mounted by the infected host. Eventually, these studies could pave the way for the development of a vaccine for syphilis, improved serological tests for the detection of syphilis, and more generally, a basic strategy for the isolation and characterization of surface protens from other pathogenic organisms that mediate infectin in a manner analogous to T. pallidum.